The establishment of this In Vivo Cellular and Molecular Imaging Center (ICMIC) will provide for multidisciplinary interactions between scientists located at the Van Andel Institute and the University of Michigan. The ICMIC will provide the framework for channeling these interactions into fully developed and novel applications in the field of molecular imaging. These interactions, which have occurred during the P20 (Pre-ICMIC) funding stage, have already yielded some of the most creative and insightful ideas in this rapidly evolving area of research termed molecular imaging. This application seeks to build upon these successful scientific interactions and experimental results in order to provide for significant advances in oncologic imaging. This group of investigators has worked diligently to bring together a uniquely integrated approach using highly novel molecular imaging constructs and imaging approaches to "report" occurrences of key cellular and molecular events. These events include carcinogenesis (Project #2), apoptosis (Project #1), activation of oncogenes (Project #3), angiogenesis (Pilot Project #1) and metastasis (Pilot Project #2). Both the initial biological event and the subsequent measured biological response can be noninvasively monitored using magnetic resonance imaging and spectroscopy (MRI/S), in vivo bioluminescence imaging (BLI) and positron emission tomography (PET). This multidisciplinary and multimodality approach will provide for a more complete understanding of the integrated events involved in the transformation process leading to tumor initiation, progression, angiogenesis, metastasis, immune response, and overall therapeutic response (or resistance). These studies will not only provide new imaging reagents and approaches for detection of these biological events, but will also yield genetically engineered mice which will have reporter genes "built-in" for noninvasively and dynamically imaging these events in intact animals over time. As mentioned above, three Research Projects and two Pilot Projects have been developed along with a Career Development Program and three Cores. The Career Development Program provides a great opportunity to train and interact with young and enthusiastic investigators in the field of molecular imaging. The Administrative Core A provides administrative support including Internal and External Scientific review for all projects. The Small Animal Imaging Core B provides the necessary expertise and imaging services including microPET, MRI, microPET in vivo BLI, autoradiography, radiopharmaceutical synthesis and digital image processing. The Transgenic Animal Core C provides the necessary expertise and centralized resources for efficient production of novel and important genetically engineered mouse imaging models. This research proposal is a natural outgrowth of the progress made with current P20 and R24 NCI support. Establishment of a world-leading ICMIC in Michigan is a priority and commitment made by the University of Michigan and the Van Andel Research Institute along with the State of Michigan (funds allocated through the Life Sciences Corridor) who have all contributed together with the NIH in order to provide the foundation necessary for ensuring the success of this vital and intriguing endeavor.